Appropriate regulation of cell proliferation and differentiation is essential for normal development and maintenance of the nervous system and for neural regeneration following disease or traumatic injury. We are studying neural regeneration in the genetic model system Drosophila melanogaster where we can manipulate neural precursors in the context of an intact brain. We have focused on the adult Drosophila mushroom body, a part of the brain that plays critical roles in learning and memory. Although the neural stem cells undergo apoptosis prior to adulthood, we have shown that the mushroom body can undergo regeneration following injury. Our working hypothesis is that certain types of glial cells adopt neural precursor fates, proliferate, and give rise to both new neurons and new glial cells. The goal of the experiments proposed in this application is to identify the cells that proliferate following injury and understand the process by which they give birth to new neurons and new glial cells. Once we have accomplished the aims described in this proposal, we will be poised to undertake further analyses of Drosophila neural regeneration, including forward genetic screens for regulators of the regenerative process. Our long-term goal is to gain sufficient knowledge of the regulatory gene networks that we can activate neural regenerative programs following disease or injury.